Brian J. Gallay

Higher surgical wound complication rates with sirolimus immunosuppression after kidney transplantation: A matched-pair pilot study

Sirolimus, a potent new immunosuppressant, has been anecdotally associated with surgical wound complications. We studied postoperative surgical wound complications in 15 kidney recipients receiving sirolimus, prednisone, and tacrolimus or cyclosporine (study group) compared with 15 recipients receiving tacrolimus, prednisone, and mycophenolate mofetil who were pair-matched for surgical wound complication risk factors. Surgical wound complications were defined as any complication related to the surgical transplant wound requiring reintervention. Fifty-three percent of the study group and 7% of the control group experienced more than one surgical wound complication (P =0.014), and the relaparotomy incidence was 33% and 7%, respectively. Four graft losses have occurred since the beginning of the study: one chronic rejection and two deaths with function in the study group, and one death with function in the control group. At 1 year, graft survival for study recipients compared with control recipients was 87% and 93%, respectively; patient survival was 93% in both groups. Recipients receiving sirolimus demonstrated a significantly higher surgical wound complication rate, but graft and patient survival were not affected. Peritransplant immunosuppression with sirolimus and steroids warrants careful consideration, particularly in recipients with surgical complication risk factors.

Pretransplant recipient cytomegalovirus seropositivity and hemodialysis are associated with decreased renal allograft and patient survival

Background. Pretransplant systemic inflammation has been associated with decreased renal allograft survival, and infectious agents such as cytomegalovi-rus (CMV) may play a role. We hypothesized that pretransplant CMV seropositivity is a risk factor for decreased patient and allograft survival after cadaveric renal transplantation and that other factors believed to modulate systemic inflammation, such as dialysis modality, might act synergistically with CMV to decrease patient and allograft survival. Methods. The United Network for Organ Sharing database was reviewed to identify all patients undergoing cadaveric renal transplantation in the United States from 1988 to 1997. Outcomes for CMV seropositive and seronegative recipients of organs from CMV seronegative donors were analyzed. Subgroup analysis was performed to identify any synergistic influence on outcome between CMV serostatus and known determinants of risk, including degree of human leukocyte antigen mismatch, pretransplant dialysis, and cold ischemia time. Results. Of 29,875 patients who underwent transplantation, 12,239 were CMV seronegative and 17,636 were CMV seropositive. Patient survival was decreased by pretransplant seropositivity (relative risk [RR] 1.11, P =0.001). In addition, this group demonstrated worse overall allograft survival (RR 1.05, P =0.029), although this adverse effect disappeared when patients who died with a functioning graft were censored. Decreased allograft survival was most pronounced in patients who were on hemodialysis before transplantation (RR 1.62, P =0.004). Conclusions. Pretransplant CMV seropositivity is associated with decreased patient survival. Pretransplant CMV seropositivity and hemodialysis have a synergistic adverse effect on graft survival, independent of patient mortality. Additional studies are required to define mechanisms by which pretransplant CMV infection and dialysis modality may contribute to decreased allograft survival.

Laryngotracheal transplantation: technical modifications and functional outcomes

Laryngeal transplantation offers the potential for patients without a larynx to recover their voice, which is critical in our communication age. We report clinical and functional outcomes from a laryngotracheal transplant. Widespread adoption of this technique has been slowed due to the ethical concerns of life‐long immunosuppression after a nonvital organ transplant. Our patient was already on immunosuppressive medication from prior kidney–pancreas transplantation, and therefore was not exposed to added long‐term risk. We describe the unique technical advances, clinical course, and rehabilitation of this patient and the implications for future laryngeal transplantation.

Efficacy of bortezomib for reducing donor-specific antibodies in children and adolescents on a steroid minimization regimen.

AMR is increasingly being recognized as an important cause of renal allograft injury, contributing to significant morbidity and graft loss. There are few controlled trials and no well‐established treatment guidelines for AMR in renal transplant recipients. We retrospectively reviewed the outcome of four pediatric renal transplant recipients on a steroid minimization immunosuppression protocol treated with bortezomib for elevated DSA and acute AMR from 2012 to 2013. All patients received four doses of bortezomib 1.3 mg/m2 given on days one, four, eight, and 11. All patients also received other treatments prior to bortezomib, which may have included rituximab, methylprednisolone, plasmapheresis, and/or IVIg. While bortezomib in addition to other therapies significantly decreased DSA titers, DSA remained very elevated months after treatment. All four patients had immediate improvement or stabilization of renal function but one eventually lost her graft. There were no adverse events related to bortezomib six months after treatment.

Fatal transplant-associated west nile virus encephalitis and public health investigation-california, 2010.

Background In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified. Methods A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology. Results Two additional recipients from the same organ donor were identified, their clinical and exposure histories were reviewed, and samples were obtained. WNV RNA was retrospectively detected in the organ donor’s serum. After transplantation, the left kidney recipient had serologic and molecular evidence of WNV infection and the right kidney recipient had prolonged but clinically inapparent WNV viremia. The liver recipient showed no clinical signs of infection but had flavivirus IgG antibodies; however, insufficient samples were available to determine the timing of infection. No remaining infectious products or tissues were identified. Conclusions Clinicians should suspect WNV as a cause of encephalitis in organ transplant recipients and report cases to public health departments for prompt investigation of the source of infection. Increased use of molecular testing and retaining pretransplantation sera may improve the ability to detect and diagnose transplant-associated WNV infection in organ transplant recipients.

Acute renal transplant injury and interaction between antithymocyte globulin and pooled human immunoglobulin.

Abstract:  The increasing number of highly sensitized patients awaiting renal transplantation has prompted the use of induction immunosuppression regimens including pooled human intravenous immunoglobulin (IVIG) combined with polyclonal anti‐lymphocyte sera. We report a case of a patient who received a live donor transplant after abrogation of donor‐specific positive cytotoxic crossmatch by IVIG. She developed early acute tubular injury associated with IVIG, mannitol, and hypertonic saline infusion. Furthermore, a possible interaction between IVIG and rabbit antithymocyte globulin (ATG) occurred, suggested by an increased number of peripheral CD3+ lymphocytes after initial rapid lymphodepletion. We suggest that IVIG‐associated nephrotoxicity should be considered in the differential diagnosis of early allograft dysfunction, and furthermore, that IVIG may interact with polyclonal antilymphocyte serum to affect the amount of lymphodepletion achieved.

Acute humoral rejection in pediatric renal transplant recipients receiving steroid minimization immunosuppression.

Butani L, Gallay BJ. Acute humoral rejection in pediatric renal transplant recipients receiving steroid minimization immunosuppression.

Angioplasty vs stent in the treatment of transplant renal artery stenosis

To compare outcomes between percutaneous transluminal angioplasty and stent placement in the treatment of transplant renal artery stenosis (TRAS).

Success of a steroid-minimization immunosuppression protocol for renal transplantation in the presence of donor-specific antibodies.

Abstract:  Steroid‐minimization regimens have gained tremendous popularity for renal Tx in the recent past since they are associated with lower metabolic complications and other adverse effects related to long‐term steroid exposure. Most such protocols have been restricted to low‐risk recipients due to the concern for acute rejection with steroid‐minimization. Herein, we report our experience in managing a child who received a positive flow cytometry cross‐match living donor kidney transplant with low titer DSA and was successfully managed using a steroid‐minimization drug regimen. The purpose of our report is to make pediatric transplant care providers aware of the feasibility of using a steroid‐minimization immunosuppression regimen even in children who have traditionally been perceived to be at higher risk for immunologic complications, allowing successful avoidance of steroid toxicity.

Elevated Parenchymal Arterial Resistive Indices After Renal Transplantation

Each month, the American Journal of Transplantation will feature Images in Transplantation, a journal-based CME activity, chosen to educate participants on current developments in the science and imaging of transplantation. Participants can earn 1 AMA PRA Category 1 CreditTM per article at their own pace. This month’s feature article is titled: “Elevated Parenchymal Arterial Resistive Indices After Renal Transplantation.”